588
BRITISH MEDICAL JOURNAL
14 JUNE 1975
Vagal Impairment of Gastric Secretion in Diabetic Autonomic Neuropathy D. J. HOSKING, FREDA MOODY, I. M. STEWART, MICHAEL ATKINSON British Medical journal, 1975,
2,
588-590
Summary Gastric acid output in response to insulin-induced hypoglycaemia and pentagastrin was measured in 18 diabetic patients with symptoms of autonomic neuropathy. Two patients had achlorhydria but the rest responded normally to pentagastrin. The acid output evoked by insulin-induced hypoglyeaemia was low in 10 of the 16 patients who secreted acid in response to pentagastrin. These changes suggest that vagal impairment is common in diabetics with autonomic symptoms, which might explain the infrequency of duodenal.ulcer in diabetics. Introduction The incidence of duodenal ulcer in diabetic patients is about a third of that in the non-diabetic population.1 2This reduced incidence is usually ascribed to a decrease in gastric secretion,3 4 which in turn has been variously attributed to gastric mucosal atrophy,5 reflected in the increased incidence of pernicious anaemia in diabetics,6 and diabetic autonomic neuropathy. Autonomic neuropathy in diabetes is thought to cause anorexia, vomiting,7 constipation, and diarrhoea,8 9 and the similarity between these symptoms and those occurring after surgical vagotomy)l supports this view. Furthermore, these alimentary symptoms are often accompanied by impotence, bladder dysfunction, or postural hypotension, which are also thought to result from autonomic disturbance. We assessed gastric acid secretion in 18 diabetics with various symptoms attributed to autonomic neuropathy using maximal stimulation with pentagastrin as a measure of parietal cell mass and the secretory response to hypoglycaemia as a measure of vagal function.
Patients and Methods After informed consent had been obtained studies of gastric acid secretion were performed on 18 diabetic outpatients. Diabetic control had been satisfactory in all patients for several months before investigation. The patients were divided into three general clinical groups on the basis of their presenting autonomic symptoms: patients in cases 1-8 suffered from diarrhoea, those in cases 9-11 from recurrent episodes of vomiting, and in cases 12-18 from impotence or bladder dysfunction. There was some overlap of symptoms: patients in cases 1-4 also suffered from vomiting, and all 10 men were impotent; only in cases 12 and 15 were there bladder symptoms. The symptoms were classified as diabetic because they showed many of the described features of autonomic neuropathy and because other aetiological factors had been excluded by investigation (table I) Laboratory procedure followed closely that described by Baron."1 Studies were performed in the morning after a 12-hour fast and
General Hospital, Nottingham NG1 6HA D. J. HOSKING, M.D., M.R.C.P., Senior Registrar FREDA MOODY, S.R.N., Nurse Technician I. M. STEWART, M.B., M.R.C.P., Medical Registrar MICHAEL ATKINSON, M.D., F.R.C.P., Consultant Physician
abstinence from smoking. With the patient in a semi-recumbent position a nasogastric tube was passed into the stomach and its position checked after five minutes by the injection and reaspiration of 20 ml of water. Patients were instructed not to swallow saliva and continuous asp;ration of gastric secretions was performed by constant hand suction. Patency of the tube was maintained by the intermittent injection of air. Gastric juice was pooled for 15-minute periods, filtered, and its volume and pH recorded. Titratable acidity was measured by titration with 0-1 M NaOH to pH 7-0, and gastric acid secretion was recorded as a concentration (mmol/l) or converted and expressed conventionally as mmol/h. TABLE I-Clinical Features of 18 Diabetics with Autonomic Neuropathy Case No.
Age and Sex
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
24 M. 38 M. 37 F. 59 M. 54 F. 66 F. 58 M. 21 F. 53 F. 56 F. 73 F. 44 M. 50 M. 37 M. 51 F. 23 M. 46 M. 45 M.
Duration of Diabetes Treatment Retinopathy Peripheral Nephropathyt Neuropathy* (Years) 7 Insulin ++ H., E. H. Insulin ++ ++ 15 + 15 Insulin N.V. + 26 Insulin + Insulin _ 45 5 CLP ++ 7 CLP B.C. + _ 14 Insulin H., E. E. M. G. 20 Insulin H. + 12 Insulin ++ + + 9 CLP _ 1 B.C. + Insulin + Insulin + 9 1 _ CLP + + 1 Insulin H., E. 11 + Insulin Insulin B.C. + 16 + 10 Insulin
* E.M.G. = Neurophysiological changes only. + = loss of ankle jerks with or without vibration sense in feet. + + = Loss of ankle and knee jerks with or without more extensive secondary loss. t + =Albuminuria. + + =Albuminuria and raised blood urea (>40 mg/100 ml). CLP = Chlorpropamnide. H. = Haemorrhages. E. = Exudates. N.V. = Neovascularizaion, B.C. = Background changes.
Insulin Dose and Blood Sugar Measurements.-Neutral insulin (Insulin Novo Actrapid) was given intravenously only after 60 minutes' basal collection of gastric secretion had been completed, and additional intravenous insulin was given 3-120 minutes after the first dose in 11 patients to lower the blood sugar level to below 2-22 mmol/l (40 mg/100 ml). Clinical signs of hypoglycaemia were seen in all patients. An indwelling venous cannula was inserted to facilitate frequent sampling for venous blood sugar concentration and provide a route for 50% dextrose solutions should they be required. Blood sugar was measured by the glucose oxidase method, but in addition rapid estimations were provided by a reflectance meter technique (Dextrostix, Ames). Blood sugar was measured after completion of the basal collection and thereafter every 15 minutes until the end of the study (at which time normoglycaemia was restored, if not already present, by intravenous or oral administration of dextrose solutions). Pentagastrin Test.-Immediately after completion of the insulin test pentagastrin 6 ,ug/kg body weight was injected subcutaneously and gastric secretion aspirated for a further 60 minutes.
Results A minimum blood sugar of
BRITISH MEDICAL JOURNAL
14 JUNE 1975
Vagal Impairment of Gastric Secretion in Diabetic Autonomic Neuropathy D. J. HOSKING, FREDA MOODY, I. M. STEWART, MICHAEL ATKINSON British Medical journal, 1975,
2,
588-590
Summary Gastric acid output in response to insulin-induced hypoglycaemia and pentagastrin was measured in 18 diabetic patients with symptoms of autonomic neuropathy. Two patients had achlorhydria but the rest responded normally to pentagastrin. The acid output evoked by insulin-induced hypoglyeaemia was low in 10 of the 16 patients who secreted acid in response to pentagastrin. These changes suggest that vagal impairment is common in diabetics with autonomic symptoms, which might explain the infrequency of duodenal.ulcer in diabetics. Introduction The incidence of duodenal ulcer in diabetic patients is about a third of that in the non-diabetic population.1 2This reduced incidence is usually ascribed to a decrease in gastric secretion,3 4 which in turn has been variously attributed to gastric mucosal atrophy,5 reflected in the increased incidence of pernicious anaemia in diabetics,6 and diabetic autonomic neuropathy. Autonomic neuropathy in diabetes is thought to cause anorexia, vomiting,7 constipation, and diarrhoea,8 9 and the similarity between these symptoms and those occurring after surgical vagotomy)l supports this view. Furthermore, these alimentary symptoms are often accompanied by impotence, bladder dysfunction, or postural hypotension, which are also thought to result from autonomic disturbance. We assessed gastric acid secretion in 18 diabetics with various symptoms attributed to autonomic neuropathy using maximal stimulation with pentagastrin as a measure of parietal cell mass and the secretory response to hypoglycaemia as a measure of vagal function.
Patients and Methods After informed consent had been obtained studies of gastric acid secretion were performed on 18 diabetic outpatients. Diabetic control had been satisfactory in all patients for several months before investigation. The patients were divided into three general clinical groups on the basis of their presenting autonomic symptoms: patients in cases 1-8 suffered from diarrhoea, those in cases 9-11 from recurrent episodes of vomiting, and in cases 12-18 from impotence or bladder dysfunction. There was some overlap of symptoms: patients in cases 1-4 also suffered from vomiting, and all 10 men were impotent; only in cases 12 and 15 were there bladder symptoms. The symptoms were classified as diabetic because they showed many of the described features of autonomic neuropathy and because other aetiological factors had been excluded by investigation (table I) Laboratory procedure followed closely that described by Baron."1 Studies were performed in the morning after a 12-hour fast and
General Hospital, Nottingham NG1 6HA D. J. HOSKING, M.D., M.R.C.P., Senior Registrar FREDA MOODY, S.R.N., Nurse Technician I. M. STEWART, M.B., M.R.C.P., Medical Registrar MICHAEL ATKINSON, M.D., F.R.C.P., Consultant Physician
abstinence from smoking. With the patient in a semi-recumbent position a nasogastric tube was passed into the stomach and its position checked after five minutes by the injection and reaspiration of 20 ml of water. Patients were instructed not to swallow saliva and continuous asp;ration of gastric secretions was performed by constant hand suction. Patency of the tube was maintained by the intermittent injection of air. Gastric juice was pooled for 15-minute periods, filtered, and its volume and pH recorded. Titratable acidity was measured by titration with 0-1 M NaOH to pH 7-0, and gastric acid secretion was recorded as a concentration (mmol/l) or converted and expressed conventionally as mmol/h. TABLE I-Clinical Features of 18 Diabetics with Autonomic Neuropathy Case No.
Age and Sex
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
24 M. 38 M. 37 F. 59 M. 54 F. 66 F. 58 M. 21 F. 53 F. 56 F. 73 F. 44 M. 50 M. 37 M. 51 F. 23 M. 46 M. 45 M.
Duration of Diabetes Treatment Retinopathy Peripheral Nephropathyt Neuropathy* (Years) 7 Insulin ++ H., E. H. Insulin ++ ++ 15 + 15 Insulin N.V. + 26 Insulin + Insulin _ 45 5 CLP ++ 7 CLP B.C. + _ 14 Insulin H., E. E. M. G. 20 Insulin H. + 12 Insulin ++ + + 9 CLP _ 1 B.C. + Insulin + Insulin + 9 1 _ CLP + + 1 Insulin H., E. 11 + Insulin Insulin B.C. + 16 + 10 Insulin
* E.M.G. = Neurophysiological changes only. + = loss of ankle jerks with or without vibration sense in feet. + + = Loss of ankle and knee jerks with or without more extensive secondary loss. t + =Albuminuria. + + =Albuminuria and raised blood urea (>40 mg/100 ml). CLP = Chlorpropamnide. H. = Haemorrhages. E. = Exudates. N.V. = Neovascularizaion, B.C. = Background changes.
Insulin Dose and Blood Sugar Measurements.-Neutral insulin (Insulin Novo Actrapid) was given intravenously only after 60 minutes' basal collection of gastric secretion had been completed, and additional intravenous insulin was given 3-120 minutes after the first dose in 11 patients to lower the blood sugar level to below 2-22 mmol/l (40 mg/100 ml). Clinical signs of hypoglycaemia were seen in all patients. An indwelling venous cannula was inserted to facilitate frequent sampling for venous blood sugar concentration and provide a route for 50% dextrose solutions should they be required. Blood sugar was measured by the glucose oxidase method, but in addition rapid estimations were provided by a reflectance meter technique (Dextrostix, Ames). Blood sugar was measured after completion of the basal collection and thereafter every 15 minutes until the end of the study (at which time normoglycaemia was restored, if not already present, by intravenous or oral administration of dextrose solutions). Pentagastrin Test.-Immediately after completion of the insulin test pentagastrin 6 ,ug/kg body weight was injected subcutaneously and gastric secretion aspirated for a further 60 minutes.
Results A minimum blood sugar of
